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妊娠女性载脂蛋白E基因型与汞浓度的关系

Apolipoprotein E genotypes in relation with Hg (MeHg) concentrations in pregnant females
课程网址: http://videolectures.net/ipssc2017_trdin_pregnant_females/  
主讲教师: Ajda Trdin
开课单位: 约瑟夫·斯特凡研究所
开课时间: 2017-05-23
课程语种: 英语
中文简介:
载脂蛋白E(apo E,gene APOE)是一种脂质结合的血浆糖蛋白,在脂质和神经元代谢中起着中心作用。一些研究人员指出它的金属结合和抗氧化性能。它有三种主要的亚型apo E2、apo E3和apo E4,分别由ε2、ε3和ε4等位基因编码。大量研究估计,ε4等位基因亚型可能与各种年龄相关的缺陷(心血管疾病、阿尔茨海默病等)有关。ε4变异的个体也更容易受到金属毒性的影响,包括甲基汞(MeHg,CH3Hg+)。另一方面,人们认为载脂蛋白E是先天免疫功能的一种全球激活剂,它与高浓度胆固醇、维生素D和钙的关联在生命早期可能是有益的。 本研究的目的是评估在怀孕期间通过食用海产品长期接触低或中等量汞的怀孕女性中,载脂蛋白E多态性与汞浓度之间的关系。 我们使用了克罗地亚孕妇(n=222,年龄19-44岁,妊娠晚期采样)及其新生儿(n=176)的样本和金属浓度数据集:母亲头发、尿液、牛奶、外周血和脐带血中的总汞和甲基汞。通过水解探针(TaqMan)预先设计的rs429358和rs7412单核苷酸多态性分析,在存档的母体白细胞DNA提取物中对APOE进行基因分型。统计:斯塔塔。欧盟项目:PHIME,治愈。 母亲被分为APOEε4携带者(ε3/ε4和ε4/ε4基因型)和ε4非携带者(ε3/ε3、ε3/ε2和ε2/ε2基因型)。其中,我们发现了17%的ε4携带者。他们的汞几何平均值显著较高:i)血液(p=0.0165;ε4携带者2.6 ng/g vs.ε4非携带者2.0 ng/g);ii)头发汞(p=0.0107;ε4携带者740 ng/g vs.ε4非携带者475 ng/g);以及iii)脐带血(p=0.0128;ε4携带者4.0 ng/g vs.ε4非携带者2.7 ng/g)。在考虑了海鲜消费、胎次、年龄、体重指数和吸烟等可能的共同因素的影响后,观察到的载脂蛋白Eε4携带者中汞浓度升高不再显著。该研究的局限性是:载脂蛋白Eε4携带者数量太少,潜在毒性元素水平低,牙科汞合金状态不完整。根据这项研究,在接触金属和营养状况范围更广的人群中,应重新考虑APOE和汞之间的正相关性。
课程简介: Apolipoprotein E (apo E, gene APOE) is a lipid binding plasma glycoprotein with central roles in lipid and neuronal metabolism. Some researchers point on its metal-binding and antioxidative properties. It has three major isoforms apo E2, apo E3, and apo E4 encoded by alleles ε2, ε3 and ε4 respectively. A large number of studies estimated, that isoform ε4 allele could be associated with various age related disadvantages (cardiovascular diseases, Alzheimer’s disease, ect). Individuals with ε4 variant are also supposed to be more susceptible to metal toxicity, including methyl mercury (MeHg, CH3Hg+). On the other hand, it is believed that apo E is a global activator of innate immune function and its association with higher concentrations of cholesterol, vitamin D and calcium can be beneficial early in life. The purpose of present work was to estimate relations between APOE polymorphisms and concentrations of mercury in pregnant females chronically exposed to low or moderate amounts of Hg through seafood consumption during pregnancy. We used samples and metal concentration data set of Croatian pregnant females (n=222, aged 19-44y, sampling in 3rd trimester) and their newborns (n=176): total Hg and MeHg in maternal hair, urine, milk, peripheral and cord blood. APOE was genotyped in archived maternal leukocytes DNA extracts by hydrolysis probes (TaqMan) pre-designed SNP assay for rs429358 and rs7412. Statistics: STATA. EU projects: PHIME, HEALS. Mothers were divided in APOE ε4 carriers (genotypes ε3/ε4 and ε4/ε4) and ε4 non-carriers (genotypes ε3/ε3, ε3/ε2 and ε2/ε2). Among them, we identified 17% of ε4 carriers. They had significantly higher geometrical means of mercury in: i) blood (p=0.0165; ε4 carriers 2.6 ng/g vs. ε4 non-carriers 2.0 ng/g), ii) hair Hg (p=0.0107; ε4 carriers 740 ng/g vs. ε4 non-carriers 475 ng/g), and iii) cord blood (p=0.0128; ε4 carriers 4.0 ng/g vs. ε4 non-carriers 2.7 ng/g). After taking into account the influence of possible cofounders like seafood consumption, parity, age, body mass index and smoking the observed higher concentrations of mercury in APOE ε4 carriers were no longer significant. Limitations of the study were: too small number of APOE ε4 carriers, low levels of potentially toxic elements and incomplete status of dental amalgams. According to that the positive associations between APOE and mercury should be reconsidered on larger population with wider ranges of metal exposure and nutritional status.
关 键 词: 载脂蛋白; 汞浓度; 等位基因编码
课程来源: 视频讲座网
数据采集: 2022-03-27:zkj
最后编审: 2022-03-27:zkj
阅读次数: 99